Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation.

BACKGROUND: Reperfusion injury after pulmonary transplantation can contribute significantly to postoperative pulmonary dysfunction. We hypothesized that posttransplantation reperfusion injury would result in an increase in both in-hospital mortality and morbidity. We also hypothesized that the incidence of reperfusion injury would be dependent upon the cause of recipient lung disease and the interval of donor allograft ischemia. METHODS: We performed a retrospective study of all lung transplant recipients at our institution from June 1990 until June 1998. One hundred patients received 120 organs during this time period. We compared two groups of patients in this study: those experiencing a significant reperfusion injury (22%) and those who did not (78%). RESULTS: In-hospital mortality was significantly greater in patients experiencing reperfusion injury (40.9% versus 11.7%, p < 0.02). Posttransplantation reperfusion injury also resulted in prolonged ventilation (393.5 versus 56.8 hours, p < 0.001) and an increased length of stay in both the intensive care unit (22.2 versus 10.5 days, p < 0.01) and in the hospital (48.8 versus 25.6 days, p < 0.03). The incidence of reperfusion injury could not be attributed to length of donor organ ischemia (221.5 versus 252.9 minutes, p < 0.20). The clinical impact of reperfusion injury was significantly greater in patients undergoing transplantation for preexisting pulmonary hypertension (6/14) than those with chronic obstructive pulmonary disease or emphysema alone (6/54) (42.9% versus 11.1%, p < 0.012). CONCLUSIONS: Clinically significant pulmonary reperfusion injury increased in-hospital mortality and morbidity resulting in prolonged ventilation, length of stay in the intensive care unit, and cost of hospitalization. The incidence of reperfusion injury was not dependent upon the duration of donor organ ischemia but increased with the presence of preoperative pulmonary hypertension. These findings suggest that recipient pathophysiology and donor allograft quality may play important roles in determining the incidence of reperfusion injury.

Replacing the atherosclerotic ascending aorta is a high-risk procedure.

BACKGROUND: Improved techniques in cerebral and myocardial protection have made replacement of the chronically aneurysmal ascending thoracic aorta a safe and effective procedure. We hypothesized that patients with severe ascending or aortic arch atherosclerosis were at greater risk for operative complications during ascending aortic replacement because of the diffuse nature of their atherosclerotic process. METHODS: We retrospectively analyzed the records of 17 patients who received ascending aortic replacement during elective coronary artery bypass grafting (CABG) because of the intraoperative finding of severe atherosclerosis. All 17 patients underwent tube graft replacement of the ascending aorta under hypothermic circulatory arrest and retrograde cerebral perfusion before coronary artery bypass grafting. The outcomes for these patients were compared with those of a control group of 89 consecutive patients who underwent replacement for ascending thoracic aortic aneurysm. RESULTS: The hospital mortality rate for replacement of the ascending thoracic aorta for severe atherosclerosis was 23.5% (4/17) versus 2.25% (2 of 89) for the control group (p=0.006). The incidence of cerebrovascular accident in the atherosclerotic group was 17.6% (3/17) and 3.37% (3/89) for the control group (p=0.051). Nine of 17 atherosclerotic patients (52.9%) had operative morbidity. Only 20.2% (18 of 89) of the control patients had nonfatal postoperative complications. CONCLUSIONS: The severely atherosclerotic ascending aorta is a marker of diffuse atherosclerosis. Despite improved techniques of myocardial and cerebral protection, we have been unable to duplicate our success with ascending thoracic aneurysm repair. Preoperative screening of the ascending aorta by chest computed tomography may be appropriate in select high-risk patients to determine operability.

Hypothermic circulatory arrest does not increase the risk of ascending thoracic aortic aneurysm resection.

OBJECTIVE: The purpose of this study was to investigate the safety and efficacy of a period of deep hypothermic circulatory arrest (DHCA) during elective replacement of the ascending thoracic aorta. SUMMARY BACKGROUND DATA: DHCA has been implemented in ascending thoracic aortic aneurysm resection whenever the anatomy or pathology of the aorta or arch vessels prevents safe or adequate cross-clamping. Profound hypothermia and retrograde cerebral perfusion have been shown to be neurologically protective during ascending aortic replacement under circulatory arrest. METHODS: The authors conducted a retrospective analysis of 91 consecutive patients who underwent repair of chronic ascending thoracic aortic aneurysms from 1986 to present. The authors hypothesized that patients undergoing DHCA with or without retrograde cerebral perfusion during aneurysm repair were at no greater operative risk than patients who received aneurysm resection while on standard cardiopulmonary bypass. RESULTS: There were no significant differences in hospital mortality, stroke rate, or operative morbidity between patients repaired on DHCA when compared to those repaired on cardiopulmonary bypass. CONCLUSIONS: DHCA with or without retrograde cerebral perfusion does not result in increased morbidity or mortality during the resection of ascending thoracic aortic aneurysms. In fact, this technique may prevent damage to the arch vessels in select cases and avoid the possible complications associated with cross-clamping a friable or atherosclerotic aorta.

Preservation with 8-bromo-cyclic GMP improves pulmonary function after prolonged ischemia.

BACKGROUND: Cyclic guanosine monophosphate (cGMP) is a potent second messenger for the nitric oxide pathway in the pulmonary vasculature. Increased cytosolic cGMP levels elicit pulmonary vasodilatation resulting in decreased pulmonary vascular resistance and maximized pulmonary function after ischemia-reperfusion injury. We hypothesized that the addition of a membrane-permeable cGMP analogue (8-bromo-cGMP) to a Euro-Collins (EC) preservation solution would ameliorate pulmonary reperfusion injury better than prostaglandin E1 injection alone after prolonged hypothermic ischemia. METHODS: All lungs from New Zealand White rabbits (weight, 3 to 3.5 kg) were harvested en bloc, flushed with EC solution, and reperfused with whole blood for 30 minutes. Group 1 lungs (immediate control) were immediately reperfused. Group 2 lungs (control) were stored inflated at 4 degrees C for 18 hours before reperfusion. Groups 3 and 4 lungs were flushed with EC solution containing 200 micromol/L 8-bromo-cGMP and stored at 4 degrees C for 18 and 30 hours, respectively. Fresh, nonrecirculated venous blood was used to determine single-pass pulmonary venous-arterial oxygen gradients at 10-minute intervals. Assays for cGMP, cyclic adenosine monophosphate, nitric oxide synthase activity, and myeloperoxidase were performed on all lung tissue samples. Wet to dry weight ratios were determined after 2 weeks of passive desiccation. RESULTS: Oxygenation (venous-arterial oxygen gradient), pulmonary artery pressure, pulmonary vascular resistance, and edema formation were significantly improved in groups 3 and 4 (addition of 8-bromo-cGMP to EC plus 18 or 30 hours of hypothermic ischemia). Hypothermic storage (groups 2, 3, and 4) decreased both nitric oxide synthase activity and myeloperoxidase levels compared with immediate reperfusion (group 1). CONCLUSIONS: These results suggest that the addition of a membrane-permeable cGMP analogue to an EC pulmonary flush solution improves pulmonary function after prolonged storage compared with EC and prostaglandin (E1) preservation alone. The finding of myeloperoxidase reduced levels after hypothermic storage and subsequent reperfusion may suggest a more important role for pulmonary hemodynamic control in mitigating pulmonary reperfusion injury.

Acellular low-potassium dextran preserves pulmonary function after 48 hours of ischemia.

BACKGROUND: We previously have shown that extracellular preservation solutions provide superior pulmonary protection after 18 hours of cold ischemia at 4 degrees C in an isolated, whole-blood-perfused, rabbit lung model. We also reported that the addition of 20% whole blood to a low-potassium dextran solution (BLPD) conferred no discernible advantage over low-potassium dextran (LPD) alone in this same model. Our current study was aimed at documenting the importance of blood in buffering extracellular preservation solutions during 24 to 48 hours of hypothermic ischemia. METHODS: We studied three groups of lungs using an isolated, whole-blood-perfused, ventilated, rabbit lung model. Lungs were flushed with Euro-Collins, LPD, or BLPD solution, and then were reperfused after 24, 36, or 48 hours of hypothermic storage at 4 degrees C. Continuous measurements of pulmonary artery pressure, pulmonary vascular resistance, left atrial pressure, tidal volume, and dynamic airway compliance were obtained. Fresh, non-recirculated venous blood was used to determine single-pass pulmonary venous-to-arterial O2 gradients. RESULTS: The 24-hour Euro-Collins group could not be completed because of immediate reperfusion failure. The 36-hour LPD group oxygenated significantly better than the 36-hour BLPD group (363.3 +/- 65.1 versus 145.3 +/- 40.3 mm Hg, respectively; p = 0.015). The 48-hour LPD group also experienced significant improvements in oxygenation when compared with the 48-hour BLPD group (pulmonary venous-arterial O2 difference of 239.4 +/- 48.4 versus 70.7 +/- 19.5 mm Hg, respectively; p = 0.012). The 48-hour LPD group also displayed significant improvements in pulmonary artery pressure (34.72 +/- 0.96 versus 55.52 +/- 7.37 mm Hg, respectively; p = 0.031) and pulmonary vascular resistance (39,737 +/- 1,291 versus 67,594 +/- 9,467 dynes.s.cm-5, respectively; p = 0.027) when compared with the 48-hour BLPD group. There were no significant differences between the three LPD groups. CONCLUSIONS: Extracellular solutions provide improved pulmonary preservation in an isolated rabbit lung model after 48 hours of cold ischemia. The addition of blood to extracellular preservation solutions diminishes pulmonary function when combined with ischemic periods of 36 to 48 hours.

Low-dose sodium nitroprusside reduces pulmonary reperfusion injury.

BACKGROUND: Reperfusion injury is a significant cause of early allograft dysfunction after lung transplantation. We hypothesized that direct pulmonary arterial infusion of an intravascular nitric oxide donor, sodium nitroprusside (SNP), would ameliorate pulmonary reperfusion injury more effectively than inhaled nitric oxide without causing profound systemic hypotension. METHODS: Using an isolated, ventilated, whole-blood-perfused rabbit lung model, we studied the effects of both inhaled and intravascular nitric oxide during lung reperfusion. Group I (control) lungs (New Zealand White rabbits, 3 to 3.5 kg) were harvested en bloc, flushed with Euro-Collins solution, and then stored inflated for 18 hours at 4 degrees C. Lungs were then reperfused with whole blood and ventilated with 60% oxygen for 30 minutes. Groups II, III, and IV received pulmonary arterial infusions of SNP at 0.2, 1.0, and 5.0 micrograms.kg-1.min-1, respectively, whereas group V was ventilated with 60% oxygen and nitric oxide at 80 ppm during reperfusion. RESULTS: Pulmonary arterial infusions of SNP even at 0.2 microgram.kg-1.min-1 (group II) showed significant improvements in pulmonary artery pressure (31.35 +/- 0.8 versus 40.37 +/- 3.3 mm Hg; p < 0.05) and pulmonary vascular resistance (38,946 +/- 1,269 versus 52,727 +/- 3,421 dynes.s/cm-5; p < 0.05) when compared with control (group I) lungs after 30 minutes of reperfusion. Infusions of SNP at 1.0 microgram.kg-1.min-1 (group III) showed additional significant improvements in dynamic airway compliance (1.98 +/- 0.10 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05), venous-arterial oxygenation gradient (116.00 +/- 24.4 versus 34.43 +/- 2.5 mm Hg; p < 0.05), and wet-to-dry ratio (6.9 +/- 0.9 versus 9.1 +/- 2.2; p < 0.05) when compared with control (group I) lungs. Lungs that received inhaled nitric oxide at 80 ppm (group V) were significantly more compliant (1.82 +/- 0.13 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05) than control (group I) lungs. CONCLUSIONS: Pulmonary arterial infusion of low-dose SNP during lung reperfusion significantly improves pulmonary hemodynamics, oxygenation, compliance, and edema formation. These effects were achieved at doses of SNP that did not cause profound systemic hypotension. Direct intravascular infusion of SNP via pulmonary arterial catheters could potentially abate reperfusion injury immediately after allograft implantation.